Scarring is a common side effect resulting from injuries and surgery. Capsular contracture is a known “side effect” commonly related with breast enhancement surgery. Capsular contracture is actually considered to be more of an exaggeration of a normal physiologic response than a side effect, and it is a thickened periprosthetic scar which engulfs the breast implant, thereby resulting in an unnaturally hard breast. Additionally, the shape of the breast can be distorted and physical pain can result from the capsular contracture.
Capsular contracture is described as an exaggerated bodily response to the insertion of the breast implant. A normal response to a breast implant is the inflammatory reaction to the implantation resulting in the formation of a collagen capsule around the implant. However, what determines the severity of the inflammatory condition is not known, but many factors are believed to contribute to the intensity of the reaction. These factors include hematoma, infection, trauma, and silicone implant leakage. Additionally, it is commonly accepted that the severity of the capsular contracture condition is increased by the acceleration or prolongation of the inflammatory condition. In other words, the longer the breast remains inflamed, the better the chances that a capsular contracture will form.
Prior to the present invention, capsular contracture was treated with breast massage, steroid irrigation, vitamin E, antibiotics, and even surgical removal of the constricted capsule.
In 1979, the term “leukotrienes” was given to a family of lipid mediators that were derived from their cell source (leukocytes). Specifically, the identification of the “slow-reacting substance of anaphylaxis (SRS-A)” lead to the identification of several additional inflammatory mediators. Arachidonic acid, a constituent of cell membranes, is released by phospholipase A2 in response to a number of biologic signals. Once released, archidonic acid can follow at least two metabolic pathways. One of these pathways is the 5-lipoxygenase pathway which gives rise to the cysteinyl leukotrienes (LTC4, LTD4, and LTE4). These are potent mediators which have been shown to cause eosinophyllic influx. Following the identification of these inflammatory mediators, efforts were placed on the development of structurally similar analogues that could modulate and perhaps halt the inflammatory process.
In November of 1996, Zeneca Pharmaceuticals introduced ACCOLATE® (zafirlukast), a leukotriene receptor antagonist (LTRA). It was approved by the Food and Drug Administration for the treatment of asthma. This class of drugs (LTRA's) possesses the unique ability to control or prevent asthma symptoms rather than the treatment of an attack once it occurs. ACCOLATE® in a dosage of 20 mg twice daily is the accepted dosage for adults and children ages 12 and up. Generally, ACCOLATE® is well tolerated, though reported side effects include headaches (12.9%) and nausea (3.1%).
Zafirlukast is disclosed in U.S. Pat. Nos. 5,612,367, 5,583,152, 4,859,692, 5,319,097, 5,294,636, 5,482,963, and 6,143,775 (which are incorporated by reference in their entirety). These patents disclose the methods of making zafirlukast, as well as methods of administering zafirlukast, and its use as a pharmaceutical agent.
Montelukast is disclosed in U.S. Pat. No. 5,565,473 (which is hereby incorporated by reference in its entirety). This patent discloses the methods of making montelukast, as well as the methods of administering the compound, and its use as a pharmaceutical agent.
Pranlukast is disclosed in U.S. Pat. No. 5,876,760 (which is hereby incorporated by reference in its entirety).
Acitanolast, verlukast, and iralukast are disclosed is U.S. Pat. No. 6,224,907 (which is herein incorporated by reference in its entirety.)
Zileuton is disclosed in U.S. Pat. No. 4,873,259 (which is hereby incorporated by reference in its entirety).